Alkystis Phinikaridou1, Prakash Saha2, Marcelo Andia3, Alberto Smith2, and René M Botnar1
1Biomedical Engineering, King's College London, London, United Kingdom, 2Academic Surgery, King's College London, London, United Kingdom, 3Radiology, Pontificia Universidad Católica de Chile, Santiago, Chile
Synopsis
Deep vein thrombosis (DVT) affects
1 in 1000 people. Its sequelae include post-thrombotic syndrome (PTS), which
affects up to 75% of patients within 5 years and is characterised
by persistent pain, swelling and ulceration. Thrombolysis can reduce PTS
by a third and is attempted in patients with an ilio-femoral DVT and symptom
onset of <3weeks. Determining age and thrombus structure by history alone
is, however, subjective and there are no established methods to quantify the
abundance of matrix proteins, which determines the response to lysis. This
treatment is therefore only effective in ~60% of patients, which may unnecessarily
exposes to haemorrhagic side effects. We have developed a non-contrast enhanced
magnetic resonance, multi-sequence thrombus imaging (MSTI) technique that can
provide information about the structural composition of experimental thrombus
[1-2]. Here, we aim in translating the MRI approach into man and determine
whether it can help guide venous
intervention.Introduction
Deep vein thrombosis
(DVT) remains an important medical condition. The biophysical characteristics of thrombus may determine the response
to endovascular interventions including lysis. We demonstrated that multi-sequence
thrombus imaging (MSTI) using magnetization transfer (MT), apparent diffusion
coefficient (ADC), and T1 mapping can characterize thrombus organization and
identify thrombi amenable to thrombolysis in a murine model [1,2]. Here, we investigate
whether MSTI can be translated to man and how these measurements associate with
the outcome of intervention.
Methods
MSTI was performed in patients (n=6, male=3, female=3, age=28-46 years
old) with ilio-femoral DVT undergoing lysis at 3T using a 32-channel coil. T2-prepared, bSSFP MR
venography (MRV) was acquired with: TR/TE=4.2/2.1ms, flip angle=70º,
FOV=220x299x200mm, matrix=112x148, slice thickness=2mm, resolution=2x2mm, averages=1,
T2-prep-echo-time=30ms. 3D T1-weighted spoiled-GRE images were acquired with
and without an on-resonance MT pre-pulse with: TR/TE=69/2.2ms, flip angle=18º,
FOV=220x299x198mm, matrix=112x148, slice thickness=6mm, resolution=2x2mm,
averages=1. The binomial-block MT pre-pulse had a duration=1.92ms and
repetitions=1. 2D diffusion weighted spin-echo images were acquired with:
TR/TE=1780/82ms, flip angle=90º, diffusion-echo-time=333ms, FOV=220x299x125mm,
matrix=112x148, slice thickness=10mm, resolution=2x2mm, averages=2 and
b-values=0, 333, 667, 1000 mm2/s. A 2D MOdified Look-Locker
Inversion Recovery (MOLLI; 3-3-5) sequence was used for T1 mapping:
TR/TE=3.3/1.6ms, flip angle=35°. FOV=220x299x198mm, matrix=112x148, slice
thickness=6mm, resolution=2x2mm, averages=1. Thrombi were segmented on all
images using Osirix and the T1, %MTR/cm3, and ADC values were
reported.
Results
MSTI is feasible in man and successful characterization of
ilio-femoral DVT was achieved in 30min. Two examples of DVT with different
compositional MRI signature that responded differentially to 24h of lytic
treatment are illustrated in Figures 1&2.
Case 1: Balanced SSFP MR venography (MRV) shows an occlusive, hypointense,
filling defect in both the Ieft external iliac vein (EIV)
and common femoral vein (CFV) (Fig. 1A-B and 1D-E). MSTI shows that the thrombus in the left EIV (Fig.
1C) and CFV (Fig. 1F) has a
short T1 relaxation time due to a high methaemoglobin concentration, low %MTR/cm3
suggestive of a loose fibrin network and low ADC values indicative of
restricted water mobility between the blood cells and fibrin meshwork. Based on
our pre-clinical data [1,2] we predicted that this thrombus would likely lyse
after treatment. In fact, 24hrs after catheter directed thrombolysis (CDT),
venography revealed a fully patent venous system (Fig. 1G).
Case 2: SSFP MR venography shows a central
hypointense thrombus in the left EIV (Fig.
2A-B) and CFV (Fig. 2D-E)
surrounded by a peri-thrombus region of high signal intensity due to vein wall
oedema. MSTI shows a long T1 relaxation time (low methaemoglobin content), high
%MTR/cm3 (dense collagen concentration) and high ADC (less
restricted mobility of water molecules within the thrombus) in both the left
EIV and CFV (Fig. 2C and 2F). These MRI findings suggest that the thrombus
is acellular and collagen-rich and mostly likely unresponsive to lysis. 24h
following CDT, venography (Fig. 2G1-G2)
demonstrated no response to lytic therapy. In this case, MSTI assessment of thrombus
composition may have prevented the unnecessary exposure of the patient to the
haemorrhagic risks associated with catheter directed thrombolysis. Quantitative
MRI data show the potential of MTR, ADC and T1 mapping in detecting
compositional differences in DVT that could be predictive of the outcome of
thrombolytic treatment (Fig. 3).
Conclusions
Non-contrast MSTI, using a combination of MTR, ADC and T1 mapping is
feasible in man and may allow characterization of thrombus composition and
understanding on how these measurements relate to the outcome of interventions.
Acknowledgements
British Heart Foundation (RG/12/1/29262 & PG/08/0392/24436)
FONDECYT 1130379
References
1. Saha P., et al. Circulation
(2013).
2. Phinikaridou A., et
al. Circulation; Cardiovasc Imaging (2013).